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Biomedical subjects

M H Johnson

Publications and source records attributed to M H Johnson.

At least 37 records · Page 2Linked to original sources

Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists.

Gleason grading is now the most widely used grading system for prostatic carcinoma in the United States. However, there are only a few studies of the interobserver reproducibility of this system, and no extensive study of interobserver reproducibility among a large number of experienced urologic pathologists exists. Forty-six needle biopsies containing prostatic carcinoma were assigned Gleason scores by 10 urologic pathologists. The overall weighted kappa coefficient kappa(w) for Gleason score for each of the urologic pathologists compared with each of the remaining urologic pathologists ranged from 0.56 to 0.70, all but one being at least 0.60 (substantial agreement). The overall kappa coefficient kappa for each pathologist compared with the others for Gleason score groups 2-4, 5-6, 7, and 8-10 ranged from 0.47 to 0.64 (moderate-substantial agreement), only one less than 0.50. At least 70% of the urologic pathologists agreed on the Gleason grade group (2-4, 5-6, 7, 8-10) in 38 ("consensus" cases) of the 46 cases. The 8 "nonconsensus" cases included low-grade tumors, tumors with small cribriform proliferations, and tumors whose histology was on the border between Gleason patterns. Interobserver reproducibility of Gleason grading among urologic pathologists is in an acceptable range.

Humans↗

Interobserver reproducibility of Gleason grading of prostatic carcinoma: general pathologist.

Only a few large studies of interobserver reproducibility of Gleason grading of prostatic carcinoma exist. Thirty-eight biopsies containing prostate cancer were distributed for Gleason grading to 41 general pathologists in Georgia. These cases had "consensus" Gleason grade groups (2-4, 5-6, 7, and 8-10) that were agreed on by at least 7 of 10 urologic pathologists. The overall kappa (kappa) coefficient for interobserver agreement for these 38 cases was 0.435, barely moderate agreement, with a kappa range from 0.00 to 0.88. There was consistent undergrading of Gleason scores 5-6 (47%), 7 (47%) and, to a lesser extent, 8-10 (25%). In cases with consensus primary patterns, there was consistent undergrading of patterns 2 (32%), 3 (39%), and 5 (30%). Pattern 2 was often (17%) mistaken for pattern 3. Pattern 4 was often undergraded (21%) and also mistaken for pattern 5 (17%). The most significant (P < .005) demographic factor associated with better interobserver agreement was having learned Gleason grading at a meeting or course. We believe that Gleason grading can be learned to a satisfactory level of interobserver reproducibility and have undertaken additional studies that support this belief.

Humans↗

Categorical perception of facial expressions by 7-month-old infants.

Recent research indicates that adults show categorical perception of facial expressions of emotion. It is not known whether this is a basic characteristic of perception that is present from the earliest weeks of life, or whether it is one that emerges more gradually with experience in perceiving and interpreting expressions. We report two experiments designed to investigate whether young infants, like adults, show categorical perception of facial expressions. 7-month-old infants were shown photographic quality continua of interpolated (morphed) facial expressions derived from two prototypes of fear and happiness. In the first experiment, we used a visual-preference technique to identify the infants' category boundary between happiness and fear. In the second experiment, we used a combined familiarisation-visual-preference technique to compare infants' discrimination of pairs of expressions that were equally physically different but that did or did not cross the emotion-category boundary. The results suggest that 7-month-old infants (i) show evidence of categorical perception of facial expressions of emotion, and (ii) show persistent interest in looking at fearful expressions.

Child, Preschool↗

tiK+ toK+: an embryonic clock?

During embryogenesis cells make appropriately timed developmental decisions. Both 'hourglass-like' and 'clock-like' mechanisms have been demonstrated to act as timers in early development. The cell cycle rhythm, using feedback circuits to drive cells unidirectionally through checkpoints, is an example of a clock-like timer, but how it operates to time developmental events is unclear. In other cell types, cyclic oscillations in K+ channel activity, which parallel cell cycle and circadian rhythms, may be part of the timing mechanism. Changes in K+ oscillations accompany key developmental transitions and oncogenic transformation. Channel blockade interferes pharmacologically with cell cycle initiation or progression, whereas channel over-expression can be oncogenic. K+ channel activity also exists in early mouse oocytes through to at least the blastocyst stage, and it oscillates in phase with the developmental cell cycles, being high in M/G1 and low in S/G2. It resembles physiologically the activity of the K+ channels of the eag- or erg-like families. Reverse transcriptase-polymerase chain reaction of mouse oocytes has revealed the presence of transcripts encoding both EAG- and ERG-like proteins throughout preimplantation development. Channel activity continues to oscillate with a cell cycle periodicity in embryos from which the nucleus has been removed, or after inhibition by puromycin of the cyclin B-cyclin-dependent kinase 1 driven component of the chromosomal cycle. Channel oscillatory activity thus appears to be able to function autonomously of the chromosomal cycle and may represent a distinct oscillatory timing activity with possible developmental significance.

Animals↗

Dendritic inhibition enhances neural coding properties.

The presence of a large number of inhibitory contacts at the soma and axon initial segment of cortical pyramidal cells has inspired a large and influential class of neural network model that use post-integration lateral inhibition as a mechanism for competition between nodes. However, inhibitory synapses also target the dendrites of pyramidal cells. The role of this dendritic inhibition in competition between neurons has not previously been addressed. We demonstrate, using a simple computational model, that such pre-integration lateral inhibition provides networks of neurons with useful representational and computational properties that are not provided by post-integration inhibition.

Algorithms↗

Sleep disorders: a risk factor for normal-tension glaucoma?

PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG). PATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures. RESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography. CONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.

Adult↗

Scleroderma "en coup de sabre": pathological evidence of intracerebral inflammation.

Linear scleroderma "en coup de sabre" (LScs) is associated with neurological complications, the pathogenesis of which is uncertain. A 27 year old woman is reported on who developed epilepsy and focal neurological signs in association with LScs. Brain MRI demonstrated predominantly ipsilateral relapsing and remitting grey and white matter lesions. Analysis of CSF and pathology obtained at brain biopsy provides evidence of an inflammatory process which may be amenable to immunosuppressive treatment.

Adult↗

Developing a disease-specific quality of life measure for people with multiple sclerosis.

OBJECTIVES: To develop a patient-completed disease-specific measure of quality of life in multiple sclerosis and to validate the measure in a community-based population of people with multiple sclerosis. METHODS: The items in the scale were selected in focus group sessions of people with multiple sclerosis. The initial scale included 25 items and was tested in subgroups of 150 people from a population register of people with multiple sclerosis in Leeds. Following further developmental phases, a restructured 16-item scale was tested on a random sample of 200 people with multiple sclerosis from the population register, stratified according to disease course. This led to a final eight-item unidimensional scale, the Leeds Multiple Sclerosis Quality of Life (LMSQoL) scale. RESULTS: After initial development a 16-item scale was found to be both reliable and valid. Cronbach's alpha for the 16-item scale was 0.86. The test-retest correlation was 0.74, using a two-week retest interval. However, convergent validity with the General Well Being Index was 0.67 and with the SF-36 Physical Function Scale was 0.68. This suggested that the scale straddled these two concepts and was confirmed by fit of the data to the Rasch measurement model. This revealed the potential for a reduced eight-item version of the scale. The eight-item scale had a closer association to well-being (0.83) than to physical function (0.39), had good internal consistency (0.79) and test-retest reliability (0.85). There were virtually no floor or ceiling effects for the scale. CONCLUSIONS: The study presents a disease-specific measure of quality of life in multiple sclerosis, the Leeds Multiple Sclerosis Quality of Life (LMSQoL) scale. The instrument is brief, easy to use and practical to administer in clinic or as a postal questionnaire. It measures a construct related to well-being, and provides an important adjunct to the measurement of outcome in multiple sclerosis.

Adult↗

Recording and analyzing high-density event-related potentials with infants. Using the Geodesic sensor net.

This article provides an overview of the use of the Geodesic sensor net system for high-density event-related potential (ERP) recording in infants. Some advantages and disadvantages of the system, as applied to infants, are discussed. First, we illustrate that high-density data can be recorded from infants at comparable quality to that observed with conventional (low density) ERP methods. Second, we discuss ways to utilize the greater spatial information available by applying source separation and localization procedures. In particular, we focus on the application of one recent source separation method, Independent Component Analysis (ICA). Finally, we show that source localization can be applied to infant high-density data, although this entails adopting a number of assumptions that remain to be verified. In the future, with improved source separation algorithms, we suggest that single-trial or single-subject analyses may become feasible.

Adult↗

Induced ovulation, mating success and embryonic development in the stripe-faced dunnart, Sminthopsis macroura.

Induced ovulation resulting in normal embryos is rare in marsupials. In this study natural and induced ovulations were compared in mature Sminthopsis macroura (n = 122). Comparison of maturation of preovulatory oocytes by ovarian histology and examination of oocytes removed from developing follicles in 12 ovaries of 23 animals receiving 0.058 iu equine serum gonadotrophin (eSG) g(-1) with ovaries of 12 animals undergoing natural cycles showed that oocyte maturation was significantly more irregular when it was induced (P < 0.001). Postovulatory stages were examined by estimating the number of eggs ovulated from ovarian histology, and by counting oviduct and uterine contents recovered after ovulation. S. macroura receiving 0.087 iu eSG g(-1) (n = 34), administered as one (n = 17) or two (n = 17) injections, were significantly (P < 0.05) more likely to ovulate (74%), mate (80%) and have conceptuses (66%) than were animals receiving 0.058 iu eSG g(-1) (12, 53 and 0%, respectively) (n = 17), and the values were similar to those in animals (n = 36) undergoing natural cycles (100, 81 and 56%, respectively). Induced ovulation using 0.087 iu eSG g(-1) yielded significantly (P < 0.05) more oocytes per ovary (20.8 +/- 8.5; combined data) than did ovulation in animals undergoing natural cycles (13.7 +/- 3.2) (ANOVA, t test). The responses of animals induced in different phases of the oestrous cycle with 0.087 iu eSG g(-1) were not significantly different (ANOVA) with respect to the number of corpora lutea per ovary, conceptuses per animal or days to ovulation after injection. However, the proportion of females that responded after receiving 0.058 iu eSG g(-1) in the luteal phase was significantly different from that in animals treated with the same dose in the intermediate phase (P < 0.01) and in non-cyclic females treated with 0.058 iu eSG g(-1) (P < 0.02). The main benefits of the treatment were that normal embryos resulted and that 70-78% of non-cyclic animals could be induced to ovulate.

Anestrus↗

External beam irradiation of subfoveal choroidal neovascularization complicating age-related macular degeneration: one-year results of a prospective, double-masked, randomized clinical trial.

OBJECTIVES: To determine the effects of low-dose external beam irradiation compared with observation on the visual function of eyes with subfoveal choroidal neovascularization (CNV) complicating age-related macular degeneration (ARMD). DESIGN: Prospective, double-masked, randomized clinical trial. Patients randomized to the radiation group received external beam irradiation at a dose of 14 Gy in 7 fractions of 2 Gy. Patients randomized to the observation group received sham radiation. SETTING: Tertiary care retinal referral practice. PATIENTS: Individuals with classic, mixed, or occult subfoveal CNV secondary to ARMD. MAIN OUTCOME MEASURES: Change in visual acuity from baseline to specified time periods. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: Forty-two eyes were randomized to observation; 41 eyes, to radiation. Baseline characteristics and demographics did not differ between groups. The median distance visual acuity (DVA) in radiation-treated eyes decreased from 20/80 at baseline to 20/320 (mean loss rate, 4.14 lines) at 1-year follow-up. The median DVA in observation group eyes decreased from 20/125 at baseline to 20/250 (mean loss rate, 3.39 lines) at 1-year follow-up. There were no statistically significant differences in changes in DVA, contrast sensitivity, or fluorescein angiographic progression from baseline between groups at any follow-up period. CONCLUSIONS: At 1-year follow-up, low-dose external beam irradiation at 14 Gy in 7 fractions of 2 Gy is neither beneficial nor harmful for subfoveal CNV complicating ARMD.

Aged↗

Gamma oscillations and object processing in the infant brain.

An enduring controversy in neuroscience concerns how the brain "binds" together separately coded stimulus features to form unitary representations of objects. Recent evidence has indicated a close link between this binding process and 40-hertz (gamma-band) oscillations generated by localized neural circuits. In a separate line of research, the ability of young infants to perceive objects as unitary and bounded has become a central focus for debates about the mechanisms of perceptual development. Here we demonstrate that binding-related 40-hertz oscillations are evident in the infant brain around 8 months of age, which is the same age at which behavioral and event-related potential evidence indicates the onset of perceptual binding of spatially separated static visual features.

Electroencephalography↗

Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12.

The distal portion of mouse chromosome 12 is imprinted. To date, however, Gtl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes multiple alternatively spliced transcripts with no apparent open reading frame. Using conceptuses with maternal or paternal uniparental disomy for chromosome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5' end of the silent paternal allele. A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the Notch signalling pathway was identified 80kb upstream of Gtl2. Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles. Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting and methylation in this domain are reminiscent of the co-ordinately regulated Igf2-H19 imprinted domain on mouse chromosome 7. Like H19 and Igf2, Gtl2 and Dlk were found to be co-expressed in the same tissues throughout development, though not after birth. These results have implications for the regulation, function and evolution of imprinted domains.

Alleles↗

Modulation of event-related potentials by prototypical and atypical faces.

High-density event-related potentials (HD-ERPs) were recorded while adults passively viewed colour images of faces that artificially (Experiment I) or naturally (Experiment II) differed in configuration. In Experiment I, altering features of faces to make them less typical and less attractive did not affect the amplitude of N170, but did affect the amplitude of P1 and P2. In Experiment II, the P1 and N170 were larger for unattractive and atypical faces compared with attractive and typical faces, in the absence of P2 effects. The results show for the first time that variations in facial configuration modulate ERP activity as early as P1, but that modulation of later latency components depends on the nature of the stimuli and implicit task demands.

Adult↗

Electrophysiological correlates of cross-linguistic speech perception in native English speakers.

The present study examined the electrophysiological responses that Native English speakers display during a passive oddball task when they are presented with different types of syllabic contrasts, namely a labial /ba/-dental /d a/, a Hindi dental /d a/-retroflex /da/ and a within-category (two /ba/ tokens) contrasts. The analyses of the event-related potentials obtained showed that subjects pre-attentively perceive the differences in all experimental conditions, despite not showing such detection behaviourally in the Hindi and within-category conditions. These results support the notion that there is no permanent loss of the initial perceptual abilities that humans have as infants, but that there is an important neural reorganisation which allows the system to overcome the differences detected and only be aware of contrasts that are relevant in the language which will become the subjects native tongue. We also report order asymmetries in the ERP responses and suggest that the percepts and not only the physical attributes of the stimuli have to be considered for the evaluation of the responses obtained.

Adult↗